Penultimate proline in neuropeptides.
Penultimate proline in neuropeptides.
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DOI：
10.1021/acs.analchem.5b01889
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发表时间：
2015-07
影响因子：
7.4
通讯作者：
Matthew S. Glover;E. Bellinger;P. Radivojac;D. Clemmer
中科院分区：
文献类型：
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作者：
Matthew S. Glover;E. Bellinger;P. Radivojac;D. Clemmer
最近的一项离子迁移谱-质谱（IMS-MS）研究表明，由于Xaa(1)-Pro(2)肽键的顺反异构化，在n端第2位含有脯氨酸残基（即倒数第二脯氨酸）的色氨酸离子经常采用多种构象[J]。点。Soc。质谱，2015,26,444]。在这里，我们提出一个神经肽数据库的统计分析，说明倒数第二脯氨酸残基经常发现在神经肽。为了探究倒数第二脯氨酸对神经肽构象的影响，我们对已知倒数第二脯氨酸残基对生物活性具有重要作用的两种模型肽进行了ms - ms实验：人类神经肽Y的n端区域(NPY1-9, Tyr(1)-Pro(2)-Ser(3)-Lys(4)-Pro(5)-Asp(6)-Asn(7)-Pro（8)-Gly(9)-NH2）和速激肽相关肽(CabTRP Ia, Ala(1)-Pro(2)-Ser(5)-Leu(6)-Gly(7)-Met（8)-Arg(9)-NH2）。从这些研究中，似乎倒数第二的脯氨酸允许神经肽填充由Xaa(1)-Pro(2)肽键的顺-反异构化产生的多种构象。虽然通常认为倒数第二脯氨酸残基的作用是保护肽免受酶降解，但目前的研究结果表明，倒数第二脯氨酸残基也是增加神经肽构象异质性的重要手段。
A recent ion mobility spectrometry-mass spectrometry (IMS-MS) study revealed that tryptic peptide ions containing a proline residue at the second position from the N-terminus (i.e., penultimate proline) frequently adopt multiple conformations, owing to the cis-trans isomerization of Xaa(1)-Pro(2) peptide bonds [J. Am. Soc. Mass Spectrom. 2015, 26, 444]. Here, we present a statistical analysis of a neuropeptide database that illustrates penultimate proline residues are frequently found in neuropeptides. In order to probe the effect of penultimate proline on neuropeptide conformations, IMS-MS experiments were performed on two model peptides in which penultimate proline residues were known to be important for biological activity: the N-terminal region of human neuropeptide Y (NPY1-9, Tyr(1)-Pro(2)-Ser(3)-Lys(4)-Pro(5)-Asp(6)-Asn(7)-Pro(8)-Gly(9)-NH2) and a tachykinin-related peptide (CabTRP Ia, Ala(1)-Pro(2)-Ser(3)-Gly(4)-Phe(5)-Leu(6)-Gly(7)-Met(8)-Arg(9)-NH2). From these studies, it appears that penultimate prolines allow neuropeptides to populate multiple conformations arising from the cis-trans isomerization of Xaa(1)-Pro(2) peptide bonds. Although it is commonly proposed that the role of penultimate proline residues is to protect peptides from enzymatic degradation, the present results indicate that penultimate proline residues also are an important means of increasing the conformational heterogeneity of neuropeptides.